Browsing by Author "Yildirim, Serkan"

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Citation - Scopus: 4
Medicinal Evaluation and Molecular Docking Study of Osajin as an Anti-Inflammatory, Antioxidant, and Antiapoptotic Agent Against Sepsis-Associated Acute Kidney Injury in Rats
(Taylor & Francis Ltd, 2024) Alhilal, Mohammad; Erol, Huseyin Serkan; Yildirim, Serkan; Cakir, Ahmet; Koc, Murat; Alhilal, Suzan; Halici, Mesut Bunyami
Despite efforts to find effective drugs for sepsis-associated acute kidney injury (SA-AKI), mortality rates in patients with SA-AKI have not decreased. Our study evaluated the protective effects of isoflavone osajin (OSJ) on SA-AKI in rats by targeting inflammation, oxidative stress, and apoptosis, which represent the cornerstones in the pathophysiological mechanism of SA-AKI. Polymicrobial sepsis was induced in rats via the cecal ligation and puncture (CLP) technique. Markers of oxidative stress were evaluated in kidney tissues using biochemical methods. The expression of interleukin-33 (IL-33), 8-hydroxydeoxyguanosine (8-OHdG), caspase-3, and kidney injury molecule-1 (KIM-1) was evaluated as indicators of inflammation, DNA damage, apoptosis, and SA-AKI respectively in the kidney tissues using immunohistochemical and immunofluorescent detection methods. The CLP technique significantly (p < 0.001) increased lipid peroxidation (LPO) levels and significantly (p < 0.001) decreased the activities of superoxide dismutase and catalase in kidney tissues. In the renal tissues, strong expression of IL-33, 8-OHdG, caspase-3, and KIM-1 was observed with severe degeneration and necrosis in the tubular epithelium and intense interstitial nephritis. In contrast, the administration of OSJ significantly (p < 0.001) reduced the level of LPO, markedly improved biomarkers of antioxidant status, decreased the levels of serum creatinine and urea, lowered the expression of IL-33, 8-OHdG, caspase-3, and KIM-1 and alleviated changes in renal histopathology. A promising binding score was found via a molecular docking investigation of the OSJ-binding mode with mouse IL-33 (PDB Code: 5VI4). Therefore, OSJ protects against SA-AKI by suppressing the IL-33/LPO/8-OHdG/caspase-3 pathway and improving the antioxidant system.
Morin Hydrate Prevents Diabetic Nephropathy by Suppressing Oxidative Stress and 8-Hydroxydeoxyguanosine in Kidney Tissues
(2025) Alhılal, Mohammad; Yildirim, Serkan; Kiliçlioğlu, Metin; Alhilal, Suzan; Esra, Dereli; Yıldırım, Hüseyin Eren
Aims: The aim of this study was to investigate the protective effect of morin hydrate either individually or in combination with metformin against diabetic nephropathy by targeting oxidative stress and 8-hydroxydeoxyguanosine (8-OHdG) in the kidney tissue of rats with diabetic nephropathy. Methods: In this experimental study, diabetic nephropathy was induced in rats by injection of streptozotocin (STZ). The ability of morin hydrate to inhibit diabetic nephropathy was tested by screening lipid peroxidation (LPO), glutathione, glutathione peroxidase, superoxide dismutase, and catalase as parameters of oxidative stress; 8-OHdG as a marker of DNA damage and kidney injury molecule-1 (KIM-1) and aquaporin as indicators of kidney injury in renal tissues; and serum creatinine and blood urea nitrogen as markers of renal function using biochemical, immunohistochemical, and immunofluorescence methods. Results: Significant increases (p<0.0001) in LPO, 8-OHdG, KIM-1, and aquaporin levels and significant decreases (p<0.0001) in glutathione, glutathione peroxidase, superoxide dismutase, and catalase levels were observed after STZ administration, indicating the development and progression of diabetic nephropathy. Treatment with morin hydrate, especially in combination with metformin, suppressed the oxidant levels and improved the antioxidant system and the histopathological integrity of the kidney, which was positively reflected in the levels of KIM-1, aquaporin, and kidney function parameters. Conclusion: Morin hydrate prevents diabetic nephropathy resulting from diabetes mellitus by suppressing oxidative stress and 8-OHdG levels in kidney tissues. Therefore, this bioflavonoid represents a promising candidate for patients with diabetic nephropathy. Moreover, the combination therapy of morin hydrate and metformin achieved better effectiveness than the single treatment, which emphasizes an important synergistic role of morin hydrate and metformin in managing patients with diabetic nephropathy.
Osajin is a Promising Candidate for Sepsis-Induced Brain Damage via Suppression of the 8-OHdG/Bax/Caspase-3 Pathway in a Rat Model of Sepsis
(2025) Erol, Huseyin Serkan; Halıcı, Mesut; Koç, Murat; Alhılal, Mohammad; Yildirim, Serkan; Kiliçlioğlu, Metin; Alhilal, Suzan
Amaçlar: Doğal ürün olan osajinin, sepsis kaynaklı beyin hasarına karşı koruyucu etkisini, sepsisli sıçanların beyin dokusundaki 8-hidroksideoksiguanozin (8-OHdG)/Bcl-2 ile ilişkili × protein (Bax)/kaspaz-3 yolunu hedef alarak inceledik. Metotlar: Osajin, Maclura pomifera'nın meyvesinden izole edilip yapısı doğrulandı. Çekal ligasyon-punksiyon (CLP) yöntemi ile sıçanlarda beyin hasarı modeli oluşturuldu. Osajin, sepsise bağlı beyin hasarı olan hayvanlara 150 ve 300 mg/kg dozlarda uygulanmıştır. Ötenazi sonrasında histopatolojik inceleme, immünohistokimya ile 8-OHdG'nin tespiti ve immünfloresan teknik kullanılarak Bax ve kaspaz-3 ekspresyonunun tahmini beyin dokusunda yapıldı. Bulgular: Histopatolojik incelemede sepsisli sıçanların beyinlerinde şiddetli düzeyde inflamasyon, belirgin dejenerasyon ve nekroz görüldü. İmmünohistokimyasal ve immünfloresan analizlerin bulguları, CLP tekniğinin, sağlıklı sıçanlarla karşılaştırıldığında sepsisli sıçanların beyin dokularında belirgin 8-OHdG, Bax ve kaspaz-3 ekspresyonunu indüklediğini ortaya çıkardı. 150 mg/kg (p < 0.05) ve 300 mg/kg (p = 0.0022) dozlarda osajin'in uygulanması, histopatolojik değişiklikleri tersine çevirdiği ve sepsisli sıçanlarla kıyaslandığında artan 8-OHdG, Bax ve kaspaz-3 ekspresyonunu önemli ölçüde iyileştirdiği gözlendi. Sonuç: Histopatolojik, immünohistokimyasal ve immünfloresan kanıtlar, osajin'in, 8-OHdG/Bax/kaspaz-3 yolunu inhibe ederek sepsisin neden olduğu beyin hasarını tersine çevirebileceğini göstermektedir. Buna göre bu doğal ürünün, sepsisli hastalardaki beyin hasarının tedavisi için umut verici bir aday olabileceği gösterilmiştir.
Probiotics Containing Lactobacillus Are Promising Candidates for Cisplatin-Induced Cardiotoxicity
(Nature Portfolio, 2025) Alhilal, Mohammad; Dabaniyasti, Eylul Turunc; Sengul, Emin; Ucar, Mahmut; Yilmaz, Ahmet; Alhilal, Suzan; Yildirim, Serkan
This study examined the effects of the mixture of probiotics Lactobacillus (Lactobacillus rhamnosus, Lactobacillus fermentum, and Lactobacillus brevis) against cardiotoxicity induced by cisplatin (CP) in rats by monitoring markers of oxidative stress, inflammation, and apoptosis in cardiac tissue. For this study, 28 male rats were divided into four groups as follows: Control, CP, Lactobacillus + CP, and Lactobacillus. Experimental cardiotoxicity was induced by CP. The activity of cardiac enzymes in serum and indicators of oxidative stress and nitric oxide (NO) in heart tissues were measured using biochemical methods. Inflammation, apoptosis, and DNA damage were also assessed in cardiac tissue by immunohistochemistry and immunofluorescence. CP administration caused a significant increases (p < 0.01) in malondialdehyde (1.53 +/- 0.21), NO (77.83 +/- 4.26), and 8-hydroxydeoxyguanosine (8-OHdG) (80.50 +/- 1.64) levels as well as marked decreases (p < 0.01) in the activity of superoxide dismutase (0.93 +/- 0.15) and the level of glutathione (1.87 +/- 0.20) in the CP group compared with those in the control group (0.88 +/- 0.19, 53.67 +/- 5.32, 21.67 +/- 0.81, 1.39 +/- 0.29, 2.64 +/- 0.28, respectively). This imbalance in the oxidant/antioxidant system was accompanied by increased expression of tumor necrosis factor-alpha (TNF-alpha), Bcl-2-associated X protein (Bax), and caspase-3. CP also caused degenerative and necrotic changes in cardiac tissues and increased cardiac biomarkers, such as serum creatine kinase, creatine kinase myocardial band, lactate dehydrogenase, and troponin I. In contrast, the Lactobacillus probiotic administration significantly reduced (p < 0.01) malondialdehyde (1.04 +/- 0.21) and NO (56.33 +/- 5.39) levels in the Lactobacillus + CP group compared with those in the CP group, and significantly increased (p < 0.01) GSH levels (2.33 +/- 0.14) in the Lactobacillus + CP group compared with that in the CP group. Lactobacillus probiotic also decreased TNF-alpha, 8-OHdG, Bax, and caspase-3 expression, and increased the expression of B-cell lymphoma 2. This enhanced the histopathology of the heart and positively affected cardiac biomarkers. In conclusion, the probiotic Lactobacillus reversed cardiotoxicity by suppressing oxidative stress, attenuating the inflammatory process, and improving the proteins that regulate apoptosis. Our findings support the use of probiotics to treat cardiotoxicity resulting from cancer therapy with CP.